Obesity is a condition characterized by an increase in body fat content resulting in excess body weight above accepted norms. Obesity is among the important nutritional disorders in the western world and can represent a major health problem in industrialized countries. This disorder can lead to increased mortality due to increased incidences of diseases such as cardiovascular disease, digestive disease, respiratory disease, cancer and type 2 diabetes. Searching for compounds, which reduce body weight has been ongoing. One line of research has included activation of serotoninergic systems, either by direct activation of serotonin receptor subtypes or by inhibiting serotonin reuptake.
Serotonin (5-hydroxytryptamine or 5-HT), a transmitter of the peripheral and central nervous system, is believed to modulate a wide range of physiological and pathological functions, including anxiety, sleep regulation, aggression, feeding and depression. Multiple serotonin receptor subtypes have been identified and cloned. One of these, the 5-HT6 receptor, displays affinity for antidepressants such as clozapine and is believed to be positively coupled to adenylyl cyclase. The effect of 5-HT6 antagonist and 5-HT6 antisense oligonucleotides is believed to be involved in the reduction of food intake in rats. Compounds believed to have enhanced affinity and selectivity for the 5-HT6 receptor have also been identified.